NIH inventors have developed P2Y1 receptor antagonists ((N)-Methanocarba 2′-Deoxyadenosine 3′, 5′-Bisphosphate Analogues) for inhibition of platelet aggregation and treatment of clotting conditions. On the platelet surface, simultaneous activation of the P2Y1 and P2Y12 receptors by ADP induces aggregation. The P2Y1-mediated response is associated with the initial shape change and rapid aggregation, and the P2Y12 receptor is associated with amplification of the aggregation. P2Y12 receptor antagonists are both in clinical use and under development as antithrombotic agents. Potent and selective P2Y1 receptor antagonists, such as the conformationally locked methanocarba nucleotide MRS2500 1 (Ki 0.79 nM), have been designed and shown to have promise in preclinical studies as antithrombotic agents. This novel drug concept is also supported by studies of mice in which the P2Y1 receptor has been genetically deleted, wherein the initiation of clotting events is markedly impaired. 0